Cristina Paradelo

Prognostic significance of molecular staging study of sentinel lymph nodes by reverse transcriptase-polymerase chain reaction for tyrosinase in melanoma patients.

BackgroundWe performed this study to evaluate the clinical effect of microscopic and submicroscopic metastases in sentinel lymph nodes (SLNs) from patients with early-stage melanoma.MethodsPatients with confirmed cutaneous melanoma (American Joint Committee on Cancer stages I and II) underwent standard lymphoscintigraphy and SLN biopsy. Serial sections were divided between routine histopathology with hematoxylin and eosin plus immunohistochemistry for HMB-45 and molecular analysis by nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase (using β-actin as a control).ResultsOf 180 patients analyzed (318 SLNs), 38 (21%) patients had positive SLN(s) by routine hematoxylin and eosin and immunohistochemistry (microscopic disease; group 1), and 142 (79%) had negative histological results. Analysis by RT-PCR detected tyrosinase in at least 1 SLN from 124 (69%) patients. Among patients with histologically negative SLN(s), tyrosinase was detected in 86 (48%) patients (submicroscopic disease; group 2), whereas 40 (22%) patients had negative results by both histology and RT-PCR (group 3). Sixteen (9%) patients had histologically negative SLNs and ambiguous RT-PCR results (group 4). Among 138 patients in the analysis of recurrence (mean follow-up, 45 months), only 18 patients had a recurrence: 11 (31%) of 35 in group 1, 5 (10%) of 51 in group 2, and 2 (5%) of 37 in group 3. No recurrences were seen in group 4. Only group 1 had a significantly shorter disease-free survival and overall survival compared with the other groups.ConclusionsAfter a long follow-up period, molecular upstaging by tyrosinase RT-PCR failed to detect a subgroup of patients with an increased probability of recurrence.

Management of Primary Cutaneous Melanoma of the Hands and Feet: A Clinicoprognostic Study

BACKGROUND Although acral lentiginous melanoma is the most common subtype of malignant melanoma in acral locations, the term acral melanoma (AM) has to be differentiated from the histopathologic description. OBJECTIVES To characterize the clinical and pathologic features of patients with a primary AM and to elucidate whether the prognosis of patients with AM differs from that of those with melanoma at other sites (nonacral melanoma; NAM). PATIENTS AND METHOD Over a 20‐year period, a series of 822 consecutive patients with melanoma were recorded in the database. Clinical and follow‐up data were retrieved from the melanoma register and prospectively analyzed. RESULTS Eighty‐nine patients had a malignant melanoma located on the acral sites of extremities. Breslow thickness and Clark level were found to be related to specific and disease‐free survival. Breslow thickness greater than 4 mm was associated with greater risk of recurrence, and amelanosis and age of 60 and older were significantly associated with greater risk of death. Comparison of survival of patients with AM with that of those with NAM clearly showed that disease‐free survival and overall survival were significantly lower in the former. CONCLUSION Survival differences between patients with AM and NAM are due to differences in already known prognostic factors, probably as a consequence of a delay in the diagnosis in these locations.

Single-Institution Experience in the Management of Patients with Clinical Stage I and II Cutaneous Melanoma: Results of Sentinel Lymph Node Biopsy in 240 Cases

Background Lymphatic mapping and sentinel lymph node biopsy (SLNB) has been developed as a minimally invasive technique to determine the pathologic status of regional lymph nodes in patients without clinically palpable disease and incorporated in the latest version of the American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma. Objective To analyze the results of SLNB and the prognostic value of the micrometastases and the pattern of early recurrences in patients according to sentinel lymph node (SLN) status. Method Patients with cutaneous melanoma in stages I and II (AJCC 2002) who underwent lymphatic mapping and SLNB from 1997 to 2003 were included in a prospective database for analysis. Results The rate of identification of the SLN was 100%. Micrometastases to SLN were found in 20.8% of patients. The rate of SLN micrometastases increased according to Breslow thickness and clinical stage. Breslow thickness of 0.99 mm was the optimal cutpoint for predicting the SLNB result. Twenty-four patients (12.3%) developed a locoregional or distant recurrence at a median follow-up of 31 months. Recurrences were more frequent in patients with a positive SLN. Among patients who had a recurrence, those with a positive SLN were more likely to have distant metastases than those with negative SLN. Nodal recurrences were more frequent in patients with a negative SLN compared with those with a positive SLN. Conclusions The status of the SLN provides accurate staging for identifying patients who may benefit from further therapy and is the most important prognostic factor of relapse-free survival.

Generalized nevus spilus and nevus anemicus in a patient with a primary lymphedema : A new type of phakomatosis pigmentovascularis?

Abstract: A patient with a generalized nevus spilus associated with a nevus anemicus and primary lymphedema is reported. We believe that this association does not reflect the merely coincidental coexistence of three kinds of anomalies but that it may represent a new type of phakomatosis pigmentovascularis.

Initial Evaluation, Diagnosis, Staging, Treatment, and Follow-up of Patients with Primary Cutaneous Malignant Melanoma. Consensus Statement of the Network of Catalan and Balearic Melanoma Centers

The consensus statement on the management of primary cutaneous melanoma that we present here was based on selection, discussion, review, and comparison of recent literature (including national and international guidelines). The protocols for the diagnosis, treatment, and follow-up used in the hospital centers throughout Catalonia and the Balearic Isles belonging to the Network of Catalan and Balearic Melanoma Centers were also considered. The main objective of this statement was to present the overall management of melanoma patients typically used in our region at the present time. As such, the statement was not designed to be an obligatory protocol for health professionals caring for this group of patients, and neither can it nor should it be used for this purpose. Professionals reading the statement should not therefore consider it binding on their practice, and in no case can this text be used to guarantee or seek responsibility for a given medical opinion. The group of dermatologists who have signed this statement was created 3 years ago with the aim of making our authorities aware of the importance of this complex tumor, which, in comparison with other types of cancer, we believe does not receive sufficient attention in Spain. In addition, the regular meetings of the group have produced interesting proposals for collaboration in various epidemiological, clinical, and basic applied research projects on the subject of malignant melanoma in our society.

Melanoma Incidence Increases in the Elderly of Catalonia But Not in the Younger Population: Effect of Prevention or Consequence of Immigration?

The remodeling of Ca2+ signaling is a common finding in cancer pathophysiology serving the purpose of facilitating proliferation, migration, or survival of cancer cells subjected to stressful conditions. One particular facet of these adaptive changes is the alteration of Ca2+ fluxes through the plasma membrane, as described in several studies. In this review, we summarize the current knowledge about the expression of different Ca2+ channels in the plasma membrane of melanoma cells and its impact on oncogenic Ca2+ signaling. In the last few years, new molecular components of Ca2+ influx pathways have been identified in melanoma cells. In addition, new links between Ca2+ homeostasis and specific cell processes important in melanoma tumor progression have been unveiled. Thus, not only do Ca2+ channels appear to have a potential as prognostic markers, but their pharmacological blockade or gene silencing is hinted as interesting therapeutic approaches.All cases of MM diagnosed in 23 hospitals in Catalonia, from 2000 to 2007 were recorded and melanoma incidence calculated and adjusted for the European standard population via the direct method. The age standardised rate/100,000 inhabitants varied from 6.74 in 2000 to 8.64 in 2007 for all melanomas and from 4.79 to 5.80 for invasive MMs; the Breslow thickness was stable during the period. The increase in invasive melanoma incidence in the elderly was remarkable, the crude rate/100,000 inhabitants increasing from 11.04 (2000) to 15.49 (2007) in the 60-64 year population, while remaining more stable in the 30-34 year range, from 3.97 in 2000 to 4.55 in 2007, and with a tendency to decrease from 5.1 in 2000 to 2.5 in 2007 for the age range of 25-29 years. These lower age ranges are much more affected by immigration. Despite the large immigrant population (nearly one million immigrants arrived in Catalonia during the study period from countries with a low melanoma incidence), melanoma incidence in our region has risen considerably and this trend is likely to persist in the near future.

The role of sentinel lymph node biopsy in the diagnosis and prognosis of malignant melanoma

Sentinel lymph node biopsy was introduced into the management of cancer patients 20 years ago. Most hospitals now currently use the technique as a routine diagnostic tool in patients with localized malignant melanoma. However, the technique is complex and numerous details need to be determined and assessed to provide reliable diagnostic and prognostic information. In addition, the introduction of immunohistochemical and molecular techniques in the last decade has extended the information provided by the study of sentinel lymph nodes and created valuable opportunities for investigating the pathogenesis of this type of cancer. The aim of this review is to offer the reader a detailed analysis of the most important studies in the literature and the factors that should currently be considered in determining the indication for sentinel lymph node biopsy, performing the procedure correctly, and interpreting the findings in patients with malignant melanoma.